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Biomolecules Sep 2022Matrix metalloproteinases (MMPs) are enzymes that decompose extracellular matrix (ECM) proteins. MMPs are thought to play important roles in cellular processes, such as... (Review)
Review
Matrix metalloproteinases (MMPs) are enzymes that decompose extracellular matrix (ECM) proteins. MMPs are thought to play important roles in cellular processes, such as cell proliferation, differentiation, angiogenesis, migration, apoptosis, and host defense. MMPs are distributed in almost all intraocular tissues and are involved in physiological and pathological mechanisms of the eye. MMPs are also associated with glaucoma, a progressive neurodegenerative disease of the eyes. MMP activity affects intraocular pressure control and apoptosis of retinal ganglion cells, which are the pathological mechanisms of glaucoma. It also affects the risk of glaucoma development based on genetic pleomorphism. In addition, MMPs may affect the treatment outcomes of glaucoma, including the success rate of surgical treatment and side effects on the ocular surface due to glaucoma medications. This review discusses the various relationships between MMP and glaucoma.
Topics: Humans; Neurodegenerative Diseases; Glaucoma; Matrix Metalloproteinases; Intraocular Pressure; Retinal Ganglion Cells; Extracellular Matrix
PubMed: 36291577
DOI: 10.3390/biom12101368 -
Cells Nov 2020The main goal of this thematic issue was to bring both original research papers and reviews together to provide an insight into the rather broad topic of molecular...
The main goal of this thematic issue was to bring both original research papers and reviews together to provide an insight into the rather broad topic of molecular biology of retinal ganglion cells (RGCs) [...].
Topics: Humans; Molecular Biology; Optic Nerve Diseases; Research; Retinal Ganglion Cells
PubMed: 33203148
DOI: 10.3390/cells9112483 -
ELife Nov 2023Neurons that transmit information from the retina to other parts of the brain are more affected by anesthesia than previously thought.
Neurons that transmit information from the retina to other parts of the brain are more affected by anesthesia than previously thought.
Topics: Retinal Ganglion Cells; Retina; Sensory Receptor Cells; Sleep
PubMed: 37947192
DOI: 10.7554/eLife.93339 -
Aging and Disease Apr 2024Aging is one of the most serious risk factors for glaucoma, and according to age-standardized prevalence, glaucoma is the second leading cause of legal blindness... (Review)
Review
Aging is one of the most serious risk factors for glaucoma, and according to age-standardized prevalence, glaucoma is the second leading cause of legal blindness worldwide. Cellular senescence is a hallmark of aging that is defined by a stable exit from the cell cycle in response to cellular damage and stress. The potential mechanisms underlying glaucomatous cellular senescence include oxidative stress, DNA damage, mitochondrial dysfunction, defective autophagy/mitophagy, and epigenetic modifications. These phenotypes interact and generate a sufficiently stable network to maintain the cell senescent state. Senescent trabecular meshwork (TM) cells, retinal ganglion cells (RGCs) and vascular endothelial cells reportedly accumulate with age and stress and may contribute to glaucoma pathologies. Therapies targeting the suppression or elimination of senescent cells have been found to ameliorate RGC death and improve vision in glaucoma models, suggesting the pivotal role of cellular senescence in the pathophysiology of glaucoma. In this review, we explore the biological links between aging and glaucoma, specifically delving into cellular senescence. Moreover, we summarize the current data on cellular senescence in key target cells associated with the development and clinical phenotypes of glaucoma. Finally, we discuss the therapeutic potential of targeting cellular senescence for the management of glaucoma.
Topics: Humans; Endothelial Cells; Glaucoma; Cellular Senescence; Retinal Ganglion Cells; Trabecular Meshwork
PubMed: 37725658
DOI: 10.14336/AD.2023.0630-1 -
Molecular Therapy : the Journal of the... Jun 2024Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights...
Glaucoma is characterized by the progressive degeneration of retinal ganglion cells (RGCs) and their axons, and its risk increases with aging. Yet comprehensive insights into the complex mechanisms are largely unknown. Here, we found that anti-aging molecule Sirt6 was highly expressed in RGCs. Deleting Sirt6 globally or specifically in RGCs led to progressive RGC loss and optic nerve degeneration during aging, despite normal intraocular pressure (IOP), resembling a phenotype of normal-tension glaucoma. These detrimental effects were potentially mediated by accelerated RGC senescence through Caveolin-1 upregulation and by the induction of mitochondrial dysfunction. In mouse models of high-tension glaucoma, Sirt6 level was decreased after IOP elevation. Genetic overexpression of Sirt6 globally or specifically in RGCs significantly attenuated high tension-induced degeneration of RGCs and their axons, whereas partial or RGC-specific Sirt6 deletion accelerated RGC loss. Importantly, therapeutically targeting Sirt6 with pharmacological activator or AAV2-mediated gene delivery ameliorated high IOP-induced RGC degeneration. Together, our studies reveal a critical role of Sirt6 in preventing RGC and optic nerve degeneration during aging and glaucoma, setting the stage for further exploration of Sirt6 activation as a potential therapy for glaucoma.
Topics: Animals; Retinal Ganglion Cells; Mice; Sirtuins; Glaucoma; Optic Nerve; Aging; Disease Models, Animal; Intraocular Pressure; Humans; Axons; Mice, Knockout; Nerve Degeneration
PubMed: 38659223
DOI: 10.1016/j.ymthe.2024.04.030 -
Cells Dec 2023Glaucoma, a leading cause of irreversible blindness globally, primarily affects retinal ganglion cells (RGCs). This review dives into the anatomy of RGC subtypes,... (Review)
Review
Glaucoma, a leading cause of irreversible blindness globally, primarily affects retinal ganglion cells (RGCs). This review dives into the anatomy of RGC subtypes, covering the different underlying theoretical mechanisms that lead to RGC susceptibility in glaucoma, including mechanical, vascular, excitotoxicity, and neurotrophic factor deficiency, as well as oxidative stress and inflammation. Furthermore, we examined numerous imaging methods and functional assessments to gain insight into RGC health. Finally, we investigated the current possible neuroprotective targets for RGCs that could help with future glaucoma research and management.
Topics: Humans; Retinal Ganglion Cells; Glaucoma; Neuroprotection
PubMed: 38132117
DOI: 10.3390/cells12242797 -
Neuron Aug 2020At various stages of the visual system, visual responses are modulated by arousal. Here, we find that in mice this modulation operates as early as in the first synapse...
At various stages of the visual system, visual responses are modulated by arousal. Here, we find that in mice this modulation operates as early as in the first synapse from the retina and even in retinal axons. To measure retinal activity in the awake, intact brain, we imaged the synaptic boutons of retinal axons in the superior colliculus. Their activity depended not only on vision but also on running speed and pupil size, regardless of retinal illumination. Arousal typically reduced their visual responses and selectivity for direction and orientation. Recordings from retinal axons in the optic tract revealed that arousal modulates the firing of some retinal ganglion cells. Arousal had similar effects postsynaptically in colliculus neurons, independent of activity in the other main source of visual inputs to the colliculus, the primary visual cortex. These results indicate that arousal modulates activity at every stage of the mouse visual system.
Topics: Animals; Arousal; Axons; Locomotion; Mice; Neurons; Optic Tract; Orientation, Spatial; Presynaptic Terminals; Retinal Ganglion Cells; Superior Colliculi; Visual Pathways; Wakefulness
PubMed: 32445624
DOI: 10.1016/j.neuron.2020.04.026 -
Cells Jul 2023This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible... (Review)
Review
This review aims to provide a better understanding of the emerging role of mitophagy in glaucomatous neurodegeneration, which is the primary cause of irreversible blindness worldwide. Increasing evidence from genetic and other experimental studies suggests that mitophagy-related genes are implicated in the pathogenesis of glaucoma in various populations. The association between polymorphisms in these genes and increased risk of glaucoma is presented. Reduction in intraocular pressure (IOP) is currently the only modifiable risk factor for glaucoma, while clinical trials highlight the inadequacy of IOP-lowering therapeutic approaches to prevent sight loss in many glaucoma patients. Mitochondrial dysfunction is thought to increase the susceptibility of retinal ganglion cells (RGCs) to other risk factors and is implicated in glaucomatous degeneration. Mitophagy holds a vital role in mitochondrial quality control processes, and the current review explores the mitophagy-related pathways which may be linked to glaucoma and their therapeutic potential.
Topics: Humans; Mitophagy; Glaucoma; Intraocular Pressure; Retinal Ganglion Cells; Mitochondria
PubMed: 37566048
DOI: 10.3390/cells12151969 -
International Journal of Molecular... Jan 2020Across all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal... (Review)
Review
Across all species, retinal ganglion cells (RGCs) are the first retinal neurons generated during development, followed by the other retinal cell types. How are retinal progenitor cells (RPCs) able to produce these cell types in a specific and timely order? Here, we will review the different models of retinal neurogenesis proposed over the last decades as well as the extrinsic and intrinsic factors controlling it. We will then focus on the molecular mechanisms, especially the cascade of transcription factors that regulate, more specifically, RGC fate. We will also comment on the recent discovery that the ciliary marginal zone is a new stem cell niche in mice contributing to retinal neurogenesis, especially to the generation of ipsilateral RGCs. Furthermore, RGCs are composed of many different subtypes that are anatomically, physiologically, functionally, and molecularly defined. We will summarize the different classifications of RGC subtypes and will recapitulate the specification of some of them and describe how a genetic disease such as albinism affects neurogenesis, resulting in profound visual deficits.
Topics: Albinism; Animals; Fibroblast Growth Factors; Hedgehog Proteins; Humans; Neurogenesis; Retina; Retinal Ganglion Cells; Transcription Factors
PubMed: 31936811
DOI: 10.3390/ijms21020451 -
Cell Reports May 2023The wiring of visual circuits requires that retinal neurons functionally connect to specific brain targets, a process that involves activity-dependent signaling between...
The wiring of visual circuits requires that retinal neurons functionally connect to specific brain targets, a process that involves activity-dependent signaling between retinal axons and their postsynaptic targets. Vision loss in various ophthalmological and neurological diseases is caused by damage to the connections from the eye to the brain. How postsynaptic brain targets influence retinal ganglion cell (RGC) axon regeneration and functional reconnection with the brain targets remains poorly understood. Here, we established a paradigm in which the enhancement of neural activity in the distal optic pathway, where the postsynaptic visual target neurons reside, promotes RGC axon regeneration and target reinnervation and leads to the rescue of optomotor function. Furthermore, selective activation of retinorecipient neuron subsets is sufficient to promote RGC axon regeneration. Our findings reveal a key role for postsynaptic neuronal activity in the repair of neural circuits and highlight the potential to restore damaged sensory inputs via proper brain stimulation.
Topics: Axons; Nerve Regeneration; Retina; Retinal Ganglion Cells; Retinal Neurons
PubMed: 37141093
DOI: 10.1016/j.celrep.2023.112476